1. Technical Field of the Invention
The present invention relates to the administration of a composition (topical medicament) comprising adapalene and benzoyl peroxide (BPO) to a patient in need so as to provide a long-term treatment of acne vulgaris.
2. Description of Background and/or Related and/or Prior Art
Acne vulgaris is a common skin disorder that makes up 20% of the visits to a dermatology practice, and affects the majority of the teenage population. Management of acne is challenging, especially when considering the chronicity of the disease and the variability in response to treatment.
The management of acne often requires combination therapy and a long-term therapeutic strategy (for example, Thiboutot D. New treatments and therapeutic strategies for acne. Arch Family Med 2000; 9: 179-187; Gollnick H, Cunliffe W, Berson D, et al., Management of acne, a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003; 49(1 suppl): S1-S37). Maintenance therapy is necessary for many acne patients, as acne lesions have been shown to recur after discontinuing a successful treatment regimen. (Gollnick H, Cunliffe W, Berson D, et al., Management of acne, a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003; 49(1 suppl): S1-S37; Thielitz A, Helmdach M, Ropke E-M, Gollnick H. Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of antiacne agents. Br J Dermatol. 2001; 145: 19-27). Long-term therapy is necessary for many acne patients to achieve the desired reduction of acne lesions as well as to increase the likelihood of maintaining short-term improvements of this commonly recurring condition (Tenaud I et al., In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions Exp. Dermatol. 2007 June; 16(6): 500-6; and Thiboutot D M et al., Treatment considerations for inflammatory acne: clinical evidence for adapalene 0.1% in combination therapies, J Drugs Dermatol. 2006 September; 5(8): 785-94. Review. Erraturn in: J Drugs Dermatol. 2007 January; 6(1):table of contents).
Despite the variety of medications available for the treatment of acute acne, there are few studies with respect to the safety and efficacy of the long-term treatment of patients with acne vulgaris.
Currently, the most effective comedolytic agents are oral isotretinoin and topical retinoids. (Cunliffe W J, Holland D B, Clark S M, Stables, G I. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol. 2000; 142: 1084-1091). Oral isotretinoin is an impractical choice for long-term therapy due to the potential for toxicity and teratogenicity. Topical anti-acne medication such as retinoids, could be associated with elevated skin irritation, so careful consideration must be given to the tolerability of a potential maintenance therapy. Cutaneous side effects may decrease the likelihood of treatment adherence, particularly when treating an asymptomatic condition. (Koo J. How do you foster medication adherence for better acne vulgaris management SKINmed. 2003; 2: 229-33; and Haider A, Shaw J C. Treatment of acne vulgaris. JAMA. 2004; 292: 726-735).
Available topical and systemic therapies for the treatment of acne include retinoids, benzoyl peroxide (BPO), antibiotics, and hormonal therapy. Since acne vulgaris involves multiple etiological factors including follicular hyperkeratinization, increased sebum production, P. acnes proliferation, and inflammation, (Thiboutot D M et al., Treatment considerations for inflammatory acne: clinical evidence for adapalene 0.1% in combination therapies, J Drugs Dermatol. 2006 September; 5(8): 785-94. Review. Erratum in: J Drugs Dermatol. 2007 January; 6(1): table of contents; Pariser D M, Westmoreland P, Morris A, Gold M H, Liu Y, Graeber M. Long-term safety and efficacy of a new fixed-dose combination of adapalene 0.1% to benzoyl peroxide 2.5% for the treatment of acne vulgaris. J Drugs Dermatol. 2007; 6(9): 899-905; Thiboutot D M, Bucko A, Eichenfield L, et al., Adapalene-benzoyl peroxide, a new fixed-dose combination for the treatment of acne vulgaris: results of a randomized, multi-centre, double-blind, controlled study. J Am Acad Dermatol. doi: 10.1016/j.jaad 2007.06.006. Published online Jul. 24, 2007) combination therapy utilizing agents with complementary mechanisms, such as a topical retinoid and an antimicrobial, is used as part of a long-term therapeutic strategy.
Current guidelines recommend early initiation of combination therapy with topical retinoids and antimicrobials for all but the most severe cases of acne, followed by topical retinoid maintenance therapy with or without benzoyl peroxide (BPO) (Thiboutot DM et al., J Drugs Dermatol. 2006 September; 5(8): 785-94. Review. Erratum in: J Drugs Dermatol. 2007 January; 6(1): table of contents). Although the administration of additional agents increases the complexity of a treatment regimen, combination therapy is effective at addressing the multifaceted pathophysiological nature of acne. Fixed-dose combination products may help reduce the complexity of acne management for patients and physicians by reducing the number of medications a patient has to remember to take on a daily basis, thereby potentially increasing treatment adherence. Despite the possible benefits, there are relatively few fixed-dose combination products available for the treatment of acne. Several BPO-antibiotic combinations are available in addition to one product that combines a topical retinoid with a topical antibiotic (Harkaway K S, McGinley K J, Foglia A N et al., Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy. Br J Dermatol. 1992; 126(6): 586-90; Thielitz A, Krautheim A, Gollnick H. Update in retinoid therapy of acne. Dermatol Ther. 2006; 19(5): 272-9; Adapalene-benzoyl peroxide, a new once daily fixed-dose combination for the treatment of acne vulgaris: a randomized, bilateral (split-face), dose-assessment study of cutaneous tolerability in healthy subjects. Cutis. Submitted).
However, there are currently no combination products with BPO and a topical retinoid, a combination that would be consistent with both the short-term and long-term treatment recommendations from the acne guidelines.
Therefore, need exists for an efficient and safe drug complying with both short term and long-term acne treatment.